From the Guidelines
The most effective diagnostic test for neuroendocrine tumors (NETs) is a combination of biochemical testing, anatomical imaging with CT or MRI, and functional imaging with somatostatin receptor scintigraphy (Octreoscan) or Gallium-68 DOTATATE PET/CT, as it offers superior sensitivity for detecting NETs 1. When diagnosing NETs, it's crucial to consider the tumor's location and the patient's clinical presentation. The initial evaluation typically involves measuring biomarkers such as chromogranin A, 5-HIAA (5-hydroxyindoleacetic acid) in 24-hour urine collection, and specific hormones depending on symptoms (insulin, gastrin, glucagon, etc.) 1.
Key Diagnostic Tests
- Biochemical testing: measuring biomarkers such as chromogranin A, 5-HIAA, and specific hormones
- Anatomical imaging: CT or MRI with contrast for localization
- Functional imaging: somatostatin receptor scintigraphy (Octreoscan) or Gallium-68 DOTATATE PET/CT for detecting NETs
- Endoscopic procedures with biopsy: often necessary for gastrointestinal NETs
- Histopathological confirmation: through biopsy or surgical specimen analysis, with immunohistochemical staining for neuroendocrine markers like synaptophysin and chromogranin The sensitivity of these diagnostic tests can vary depending on the type of NET and its location. For example, somatostatin receptor scintigraphy (SSRS) has a sensitivity of up to 90% for detecting foregut, midgut, and hindgut tumors, while CT scans are more effective for localizing lung lesions 1.
Sensitivity of Diagnostic Tests
- SSRS: up to 90% for foregut, midgut, and hindgut tumors
- CT scans: best modality for localizing lung lesions
- EUS: major diagnostic investigation for pancreatic NETs, with a sensitivity of 80% for gastric tumors
- Angiography with calcium stimulation: 93% sensitivity for detecting gastrinomas It's essential to tailor the diagnostic approach to the suspected tumor location and clinical presentation, as NETs can arise in various organs and present with diverse symptoms based on hormone production and tumor burden 1.
From the Research
Diagnostic Tests for Neuroendocrine Tumors
- The diagnosis of neuroendocrine tumors (NETs) relies on a combination of biochemical markers, computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin-receptor based functional imaging 2.
- Somatostatin receptor scintigraphy (SRS) using single photon emission tomography (SPECT) is a well-established standard in molecular imaging of NETs, and can be used in combination with structural imaging (hybrid imaging) to provide functional information about the tumor 3.
- Positron emission tomography (PET) with somatostatin analogues, such as gallium-68, is a more sensitive technique than SRS and can be used to identify additional lesions not visible on CT or MRI scans 4.
- Functional imaging with octreotide scan or gallium-68 somatostatin analog PET can be used selectively to confirm diagnosis and guide therapy 5.
- In cases of poorly differentiated neuroendocrine cancers, 18F-FDG PET/CT may be beneficial in comparison with molecular imaging based on somatostatin receptor modalities 3, 4.
Imaging Modalities
- CT and MRI are well-suited for discerning small lesions and assessing the local invasiveness of the tumor or the response to therapy 4.
- Somatostatin receptor imaging, by (111)In-pentetreotide scintigraphy or PET with (68)Ga-labelled somatostatin analogues, can frequently identify additional lesions that are not visible on CT or MRI scans 4.
- PET-CT with (18)F-dihydroxy-L-phenylalanine or (11)C-5-hydroxy-L-tryptophan is a useful problem-solving tool and could be considered for the evaluation of therapy response in the future 4.
Limitations and Future Directions
- Somatostatin receptor imaging has some limitations, such as relatively low detection rate of benign insulinomas, poorly differentiated GEP-NETs, and liver metastases 3.
- Further improvement of NETs imaging is necessary, and new tracers' families based on SSTR antagonists, 64Cu-radiolabeled ligands, and glucagon-like peptide-1 receptor (GLP-1R) imaging are being developed 3.
- Novel functional imaging modalities are likely to be developed to detect small NETs, predict prognosis, guide therapeutic choices, and design novel therapies 5.